Immunoregulatory Effects of the Active Form of Vitamin D (Calcitriol), Individually and in Combination with Curcumin, on Peripheral Blood Mononuclear Cells (PBMCs) of Multiple Sclerosis (MS) Patients.

OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease affecting the central nervous system. Immune cell subsets, notably T helper (Th) 17 and Th1, exert important roles in MS pathogenesis. Whereas, Treg cells modulate the disease process. Calcitriol, the active form of vitamin D, and curcumin, a bioactive compound derived from turmeric, play immunomodulatory effects relevant to autoimmune disorders, including MS. The objective of this study is to investigate the effects of calcitriol and Curcumin on Peripheral blood mononuclear cells (PBMCs) of individuals with MS. METHODS: PBMCs from twenty MS patients were isolated, cultured, and exposed to 0.004 µg/mL of calcitriol and 10 µg/mL of curcumin. The cells underwent treatment with singular or combined doses of these components to assess potential cumulative or synergistic immunomod-ulatory effects. Following treatment, the expression levels of genes and the cellular population of Treg, Th1 and Th17 were evaluated using Real-time PCR and flow cytometry. RESULTS: Treatment with curcumin and calcitriol led to a significant reduction in the expression levels of inflammatory cytokines and transcription factors related to Th1 and Th17 cells, includ-ing IFN-γ, T-bet, IL-17, and RORC. Furthermore, the frequency of these cells decreased follow-ing treatment. Additionally, curcumin and calcitriol treatment resulted in a significant upregu-lation of the FOXP3 gene expression and an increase in the frequency of Treg cells. CONCLUSION: This study demonstrates that curcumin and calcitriol can effectively modulate the inflammatory processes intrinsic to MS by mitigating the expression of inflammatory cytokines by Th1 and Th17 cells while concurrently enhancing the regulatory role of Treg cells. Moreover, the combined treatment of curcumin and calcitriol did not yield superior outcomes compared to single-dosing strategies.

Phoenix dactylifera L. pollen versus pentoxifylline on improvement of sperm parameters in idiopathic male infertility: A randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Phoenix dactylifera L. pollen is the male reproductive dust of palm flowers known as a natural product that is considered a strong stimulant of sexual potency and fertility in Iranian traditional medicine (ITM). In this regard, no evidence-based medications are empirically prescribed to treat IMI. However, applying traditional medicine for the treatment of male infertility has attracted more attention in recent years. AIM OF THE STUDY: Phoenix dactylifera L. pollen was compared with pentoxifylline (PTX) to evaluate its efficacy on sperm parameters. MATERIALS AND METHODS: During this parallel randomized controlled trial, 80 adult men with asthenozoospermia, oligozoospermia, or teratozoospermia (age 20-35 years) were enrolled. In two separate groups of participants with a 1:1 ratio, participants received either 6 g of Phoenix dactylifera L. pollen powder daily or 400 mg of PTX tablets daily for 90 days. We measured the sperm parameters as well as the serum sex hormones in the sample. ANCOVA and t-tests were used to compare groups. RESULTS: There was no significant difference between the study groups in terms of baseline characteristics or demographic characteristics. According to the results, participants who took Phoenix dactylifera L. pollen powder had significantly improved sperm concentration (p = 0.016), morphology (p = 0.029), sperm counts (p = 0.012), progressive motility (p = 0.016), total motility (p = 0.018), and reduced immotile sperms (p = 0.014) compared to those who took PTX. CONCLUSIONS: In light of these results, Phoenix dactylifera L. pollen is recommended as a treatment factor for ameliorating IMI by enhancing sperm functional capacity and semen parameters.

The effect of different types of cognitive tasks on postural sway fluctuations in older and younger adults: A nonlinear study.

BACKGROUND: There are numerous types of cognitive tasks classified as mental tracking (MT), working memory (WM), reaction time (RT), discrimination and decision-making and verbal fluency (VF). However, limited studies have investigated the effects of cognitive task type on postural control in older adults. PURPOSE: s: The aim of this study was to investigate the effect of aging and several types of cognitive tasks on postural control in terms of nonlinear analysis. METHOD: Postural control was investigated under 6 conditions (single task and dual-task with RT; easy and difficult VF; easy and difficult WM; easy and difficult MT. Outcome measurements were the max Lyapunov, entropy, and correlation dimension at anteroposterior (AP) and mediolateral (ML) directions. RESULTS: The results revealed that within the older group, the AP & ML max Lyapunov at dual-task with difficult WM and MT was significantly higher than all other conditions. In addition, the older group had lower AP entropy at dual-task with easy VF, difficult WM, and easy as well as difficult MT. CONCLUSION: The results can be useful to understand the postural control mechanisms and to detect the alterations following aging and applying different types of cognitive tasks. In addition, the investigated parameters can be a basis for identifying postural control deficiencies.

The effects of Annual SZ drug on dynamic changes in lymphocytes and cytokines of COVID-19 patients: A randomized clinical trial.

BACKGROUND: The search for a potent anti-coronavirus therapy has remained an overwhelming task since the outbreak of COVID-19. Annual SZ is a novel formulation of artemisinin and its derivatives. We aim to investigate the effect of Annual SZ on clinical outcomes, cellular immune responses, and cytokine changes in COVID-19 patients. METHODS: This study included 80 COVID-19 hospitalized patients, which were randomly allocated into two groups (intervention and control). Both groups received standard supportive treatment. In addition, the intervention group (n = 40) received Annual SZ syrup, and the control group (n = 40) received a placebo. Dynamic changes in lymphocytes, cytokines, and clinical status were evaluated since hospital admission to 7 and 14 days after treatment. RESULTS: The dynamic count of total T lymphocytes and T lymphocyte subsets (CD4+ and CD8+) in the Annual SZ group was significantly higher than the placebo group (p < 0.05). In addition, Programmed Death 1 (PD-1) was significantly increased in the CD4+ and CD8+ T cells in the placebo group compared with the Annual SZ group (p < 0.05). Also, the CD4+/CD8+ ratio was not significantly different between the groups (p > 0.9). Moreover, IL-6 levels were significantly reduced (p < 0.05), while IL-4 and IFN-γ levels were not statistically different between the two groups (p > 0.05). CONCLUSION: This research indicated that the Annual SZ syrup significantly improved clinical status and lymphocyte frequency with less exhaustion of T lymphocytes and a reduction of inflammatory responses, which seems to be beneficial in the treatment process of COVID-19 patients.

Associations between food insecurity and Sleep Duration, Quality, and Disturbance among older adults from six low- and middle-income countries.

OBJECTIVES: Although food insecurity has been associated with poor sleep outcomes in young and middle-aged adults, few studies have examined this relationship in older adults. This study aimed to examine the relationship between food insecurity and sleep duration, quality, and disturbance among older adults in six low-income countries (LMICs). DESIGN AND SETTING: We analyzed nationally representative cross-sectional data from 33,460 adults (≥50 years) from the Study on global AGEing and adult health (SAGE). MEASUREMENTS: Food insecurity (FI) was assessed using two questions regarding the frequency of eating less and hunger caused by a lack of food. Sleep outcomes included self-reported sleep duration, sleep quality, and sleep disturbances (difficulty falling asleep, frequent sleep interruptions, and early awakening) assessed based on self-reports over two nights. Multivariable logistic regression was used to assess country-specific relationships between food insecurity and sleep outcomes, and random-effects models were used to estimate pooled associations. RESULTS: The prevalence of FI among older adults in the overall population was 16.2%. In pooled analyses, FI was significantly associated with long sleep duration ≥ 9 h (OR=1.58, 95% CI: 1.30 to 1.93; P=0.001). There were also significant pooled associations between FI and poor sleep quality (OR=1.34, 95% CI: 1.14 to 1.56; P < 0.001) and sleep disturbances (OR=1.44, 95% CI: 1.08 to 1.91; P = 0.014). CONCLUSIONS: In conclusion, the current study found that FI is adversely associated with sleep duration, quality and disturbances in older adults, with some heterogeneity by country. The findings suggest food policies and intervention programs are needed for vulnerable households.

A higher number of exhausted local PD1+, but not TIM3+, NK cells in advanced endometriosis.

Endometriosis (EMT) is a chronic inflammatory disease characterized by the presence and growth of endometrial-like glandular epithelial and stromal cells outside the uterus. Natural Killer (NK) cell dysfunction/exhaustion has been shown in patients with EMT. In this case-control study, we compared the frequency of exhausted PD-1 or TIM-3 positive NK cells in peripheral blood (PB) and peritoneal fluid (PF) of women with advanced endometriosis to control fertile women. PB and PF were collected from women aged 25-40 who underwent the laparoscopic procedure, including 13 stages III/IV endometriosis and 13 control samples. Multicolor flowcytometry was used to compare the frequency of PD-1 or TIM-3 positive NK (CD3-CD56+) cells in PB and PF of two groups. We demonstrated a higher percentage of PD-1+ NK cells in the peritoneal fluid of patients with endometriosis rather than controls (P-value = 0.039). This significance was related to stage IV of endometriosis (P-value = 0.047). We can not show any significant difference in the number of PD-1 or TIM-3 positive NK cells in peripheral blood. Our results suggest a local exhausted NK cell response in endometriosis that can be a leading factor in the endometriosis pathogenesis.

The interaction between MALAT1 and TUG1 with dietary fatty acid quality indices on visceral adiposity index and body adiposity index.

We aimed to investigate the interaction between the transcript levels of taurine-upregulated gene 1 (TUG1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the Cholesterol-Saturated Fat Index (CSI) in relation to the visceral adiposity index (VAI) and body adiposity index (BAI). This cross-sectional study involved 346 women classified as obese and overweight, aged between 18 and 48 years. Dietary intake and the quality of dietary fat were assessed using a validated and reliable 147-item semi-quantitative food frequency questionnaire, with the Cholesterol-Saturated Fat Index (CSI) used as an indicator. Transcription levels of MALAT1 and TUG1 were evaluated through real-time polymerase chain reaction following the criteria outlined in the Minimum Information for Publication of Quantitative standards. Serum profiles were measured using standard protocols. We observed a positive association between transcription level of MALAT1 and VAI in both crude (ß = 3.646, 95% CI 1.950-5.341, p < 0.001) and adjusted (ß = 8.338, 95% CI 6.110-10.566, p < 0.001) models. Furthermore, after adjusting for confounders, a significant positive interaction was noted between MALAT1 expression and CSI on BAI (ß: 0.130, 95% CI 0.019, 0.240, p = 0.022), with a marginal positive interaction observed on VAI (ß: 0.718, 95% CI - 0.028, 1.463, p = 0.059). It seems that there may be a positive interaction between MALAT1 transcription level and CSI on VAI and BAI among overweight and obese women. However, no associations were seen between TUG1 mRNA level and the above-mentioned outcomes. Further functional studies are still required to elucidate this concept.

Exploring health literacy categories among an Iranian adult sample: a latent class analysis.

General and electronic health literacy are important factors engaging in healthy behaviors and maintaining good health. The present study explored demographic factors associated with general and electronic health literacy in the Iranian adult population. Via stratified cluster sampling, trained interviewers visited adult residents in Qazvin Province, Iran between January, and April 2022. The participants (N = 9775; mean age = 36.44 years; 6576 [67.3%] females) completed the Health Literacy Instrument for Adults (HELIA) assessing health literacy and the eHealth Literacy Scale (eHEALS) assessing electronic health literacy. Demographic data, including age, gender, educational level, marital status, and living location (city or rural), were collected. Latent class analysis (LCA) was used to classify the participants into different health literacy/electronic health literacy levels. The relationships between health literacy/electronic health literacy levels and demographic factors were examined using χ2 or analysis of variance. The LCA used HELIA scores to suggest five classes of health literacy and eHEALS scores to suggest three classes of electronic health literacy. For general and electronic health literacy, similar relationships were with demographic factors: females as compared with males had better general/electronic health literacy; younger people as compared with older people had better general/electronic health literacy; higher educational level was associated with better general/electronic health literacy; and city residents as compared with rural residents had better general/electronic health literacy. In conclusion, Iranian governmental agencies may wish to target on males, older adults, people with low educational level, and rural residents to improve their health literacy.

Machine Learning Models for Predicting Sudden Sensorineural Hearing Loss Outcome: A Systematic Review.

BACKGROUND: Machine Learning models have been applied in various healthcare fields, including Audiology, to predict disease outcomes. The prognosis of sudden sensorineural hearing loss is difficult to predict due to the variable course of the disease. Hence, researchers have attempted to utilize ML models to predict the outcome of patients with sudden sensorineural hearing loss. The objectives of this study were to review the performance of these machine learning models and assess their applicability in real-world settings. METHODS: A systematic search was conducted in PubMed, Web of Science and Scopus. Only studies that built machine learning prediction models were included, and studies that used algorithms such as logistic regression only for the purpose of adjusting for confounding variables were excluded. The risk of bias was assessed using the Prediction model Risk of Bias Assessment Tool (PROBAST). RESULTS: After screening, a total of 7 papers were eligible for synthesis. In total, these studies built 48 ML models. The most common utilized algorithms were Logistic Regression, Support Vector Machine (SVM) and boosting. The area under the curve of the receiver operating characteristic curve ranged between 0.59 and 0.915. All of the included studies had a high risk of bias; hence there are concerns regarding their applicability. CONCLUSION: Although these models showed great performance and promising results, future studies are still needed before these models can be applied in a real-world setting. Future studies should employ multiple cohorts, different feature selection methods, and external validation to further validate the models' applicability.

Immunoregulatory Effect of Calcitriol on Experimental Autoimmune Encephalomyelitis (EAE) Mice.

Previous studies noted an imbalance in T helper (Th) 17 and regulatory T cells (Tregs) in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis animal model. calcitriol, vitamin D's active form, was found to ameliorate EAE symptoms by favoring Tregss over Th17 cells, suggesting immunomodulatory effects. This study aimed to assess calcitriol's impact on EAE manifestations and cytokine profile in mice. In this study, we recruited twenty-eight C57BL/6 mice and divided them into 4 groups: healthy controls, EAE, EAE with calcitriol treatment, and healthy mice with calcitriol treatment. CD4+ T cells were isolated from splenocytes using magnetic-activated cell sorting. Real-time polymerase chain reaction was employed to quantify the genes associated with Th9 cells (i.e., SPI1 encoding PU.1 and IL9 encoding interleukin [IL]-9). Moreover, the levels of IL-17 and transforming growth factor beta (TGF-ß) were evaluated through enzyme-linked immunosorbent assay in the supernatant of CD4+ T cell culture stimulated by anti-CD3 and anti-CD28 antibodies for 72 hours. In the supernatant of CD4+ T cell cultures, the levels of interleukin-17 (IL-17) were significantly increased, while the levels of transforming growth factor beta (TGF-ß) were decreased in the EAE Group compared to the healthy control group. Calcitriol treatment reversed these changes and attenuated EAE symptoms, as confirmed in hematoxylin and eosin, and luxol fast blue stains. Notably, calcitriol increased IL9 gene expression in both EAE and healthy mice.  This study provides further evidence of the anti-inflammatory effects of calcitriol and its role in attenuating EAE.

Mental health outcomes of hospital staff during the COVID-19 pandemic in Iran.

BACKGROUND: The COVID-19 pandemic, which had recorded 769 million cases and resulted in 6.95 million deaths by August 2023, has put pressure on healthcare systems. Frontline medical professionals face stress, potentially leading to health challenges. This research aimed to examine the mental health of staff during the COVID-19 pandemic. METHODS: This cross-sectional descriptive-analytical study was conducted in several hospitals in Tehran, Kerman, and Golpayegan between 2021 and 2022. The study encompassed a population of 1,231 nurses and physicians. Data collection was done using the General Health Questionnaire-28 (GHQ-28). We applied the K-means clustering algorithm to unveil hidden patterns within the data and extract valuable insights from participants' responses to the GHQ-28. This method was chosen because our dataset lacked explicit labels, making grouping individuals with similar characteristics necessary. The primary aim was to delineate how the COVID-19 pandemic affected the mental health of hospital staff and identify which factors played a more significant role in this process. RESULTS: We have observed that Cluster two exhibits the highest scores in response to the GHQ-28 questions, indicating a more significant degree of mental distress. Within this cluster, 83.0% of individuals identify as female, 71.0% hold bachelor's degrees and 42.8% are nurses who have experienced the most substantial impact. Among these individuals, 90.4% did not have a history of smoking. Additionally, 59.7% are married, suggesting that these mental health issues may also affect their families. CONCLUSION: Given that the most critical subscale is related to anxiety/insomnia within the second cluster, it is necessary to implement management plans aimed at appropriately redistributing night shifts to improve employee health.

Predicting the COVID-19 mortality among Iranian patients using tree-based models: A cross-sectional study.

Background and Aims: To explore the use of different machine learning models in prediction of COVID-19 mortality in hospitalized patients. Materials and Methods: A total of 44,112 patients from six academic hospitals who were admitted for COVID-19 between March 2020 and August 2021 were included in this study. Variables were obtained from their electronic medical records. Random forest-recursive feature elimination was used to select key features. Decision tree, random forest, LightGBM, and XGBoost model were developed. Sensitivity, specificity, accuracy, F-1 score, and receiver operating characteristic (ROC)-AUC were used to compare the prediction performance of different models. Results: Random forest-recursive feature elimination selected following features to include in the prediction model: Age, sex, hypertension, malignancy, pneumonia, cardiac problem, cough, dyspnea, and respiratory system disease. XGBoost and LightGBM showed the best performance with an ROC-AUC of 0.83 [0.822-0.842] and 0.83 [0.816-0.837] and sensitivity of 0.77. Conclusion: XGBoost, LightGBM, and random forest have a relatively high predictive performance in prediction of mortality in COVID-19 patients and can be applied in hospital settings, however, future research are needed to externally confirm the validation of these models.

Reverse vaccinology approaches to introduce promising immunogenic and drug targets against antibiotic-resistant Neisseria gonorrhoeae: Thinking outside the box in current prevention and treatment.

Gonorrhea is an urgent antimicrobial resistance threat and its therapeutic options are continuously getting restricted. Moreover, no vaccine has been approved against it so far. Hence, the present study aimed to introduce novel immunogenic and drug targets against antibiotic-resistant Neisseria gonorrhoeae strains. In the first step, the core proteins of 79 complete genomes of N. gonorrhoeae were retrieved. Next, the surface-exposed proteins were evaluated from different aspects such as antigenicity, allergenicity, conservancy, and B-cell and T-cell epitopes to introduce promising immunogenic candidates. Then, the interactions with human Toll-like receptors (TLR-1, 2, and 4), and immunoreactivity to elicit humoral and cellular immune responses were simulated. On the other hand, to identify novel broad-spectrum drug targets, the cytoplasmic and essential proteins were detected. Then, the N. gonorrhoeae metabolome-specific proteins were compared to the drug targets of the DrugBank, and novel drug targets were retrieved. Finally, the protein data bank (PDB) file availability and prevalence among the ESKAPE group and common sexually transmitted infection (STI) agents were assessed. Our analyses resulted in the recognition of ten novel and putative immunogenic targets including murein transglycosylase A, PBP1A, Opa, NlpD, Azurin, MtrE, RmpM, LptD, NspA, and TamA. Moreover, four potential and broad-spectrum drug targets were identified including UMP kinase, GlyQ, HU family DNA-binding protein, and IF-1. Some of the shortlisted immunogenic and drug targets have confirmed roles in adhesion, immune evasion, and antibiotic resistance that can induce bactericidal antibodies. Other immunogenic and drug targets might be associated with the virulence of N. gonorrhoeae as well. Thus, further experimental studies and site-directed mutations are recommended to investigate the role of potential vaccine and drug targets in the pathogenesis of N. gonorrhoeae. It seems that the efforts for proposing novel vaccines and drug targets appear to be paving the way for a prevention-treatment strategy against this bacterium. Additionally, a combination of bactericidal monoclonal antibodies and antibiotics is a promising approach to curing N. gonorrhoeae.

Principal component analysis of adipose tissue gene expression of lipogenic and adipogenic factors in obesity.

OBJECTIVE: A better understanding of mechanisms regulating lipogenesis and adipogenesis is needed to overcome the obesity pandemic. We aimed to study the relationship of the transcript levels of peroxisome proliferator activator receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBP-α), liver X receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese and normal-weight women with a variety of anthropometric indices, metabolic and biochemical parameters, and insulin resistance. METHODS: Real-time PCR was done to evaluate the transcript levels of the above-mentioned genes in VAT and SAT from all participants. RESULTS: Using principal component analysis (PCA) results, two significant principal components were identified for adipogenic and lipogenic genes in SAT (SPC1 and SPC2) and VAT (VPC1 and VPC2). SPC1 was characterized by relatively high transcript levels of SREBP1c, PPARγ, FAS, and ACC. However, the second pattern (SPC2) was associated with C/EBPα and LXR α mRNA expression. VPC1 was characterized by transcript levels of SREBP1c, FAS, and ACC. However, the VPC2 was characterized by transcript levels of C/EBPα, LXR α, and PPARγ. Pearson's correlation analysis showed that unlike SPC2, which disclosed an inverse correlation with body mass index, waist and hip circumference, waist to height ratio, visceral adiposity index, HOMA-IR, conicity index, lipid accumulation product, and weight-adjusted waist index, the VPC1 was positively correlated with above-mentioned obesity indices. CONCLUSION: This study provided valuable data on multiple patterns for adipogenic and lipogenic genes in adipose tissues in association with a variety of anthropometric indices in obese subjects predicting adipose tissue dysfunction and lipid accumulation.

Assessment of quality of life and self-esteem in male patients with androgenetic alopecia before and after hair transplantation.

BACKGROUND: Patients with androgenetic alopecia experience a significant decrease in self-esteem and quality of life. There are several methods by which these factors may be improved. AIMS: Determining whether patients feel better about themselves with a better quality of life after undergoing hair transplant procedure. PATIENTS/METHODS: 35 people were chosen from Jordan Skin and Hair Clinic in Tehran, Iran. Following hair transplant, follow-up subjects had their quality of life and level of self-esteem assessed using the Rosenberg Self-Esteem Scale (RSES) and Dermatology Life Quality Index (DLQI), respectively. The means of quantitative results were compared using paired T-test. The chi-square test was done to compare preoperative and postoperative characteristics qualitatively. Differences were regarded significant if p < 0.05. Analysis of covariance was applied to evaluate the effect of marital status and educational level on outcome variables (ANCOVA). RESULTS: Our findings showed a statistically significant difference (p < 0.001) between pre- and post-operative hair transplantation for quality of life, and mean score increased to 2.17. There was a statistically significant difference between the two groups, with an average self-esteem score on RSES rising to 5.35 (p < 0.001). A statistically significant link between educational achievement and quality of life was found (p < 0.001). CONCLUSION: This study found postoperative psychological aspects of AGA patients significantly improve than preoperative. Our results show that there is a statistically significant difference between the self-esteem and quality of life of AGA patients before and after hair restoration surgery.

Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis.

Background: Breast cancer (BC) is the most common cancer in women. The incidence and morbidity of BC are expected to rise rapidly. The stage at which BC is diagnosed has a significant impact on clinical outcomes. When detected early, an overall 5-year survival rate of up to 90% is possible. Although numerous studies have been conducted to assess the prognostic and diagnostic values of non-coding RNAs (ncRNAs) in breast cancer, their overall potential remains unclear. In this field of study, there are various systematic reviews and meta-analysis studies that report volumes of data. In this study, we tried to collect all these systematic reviews and meta-analysis studies in order to re-analyze their data without any restriction to breast cancer or non-coding RNA type, to make it as comprehensive as possible. Methods: Three databases, namely, PubMed, Scopus, and Web of Science (WoS), were searched to find any relevant meta-analysis studies. After thoroughly searching, the screening of titles, abstracts, and full-text and the quality of all included studies were assessed using the AMSTAR tool. All the required data including hazard ratios (HRs), sensitivity (SENS), and specificity (SPEC) were extracted for further analysis, and all analyses were carried out using Stata. Results: In the prognostic part, our initial search of three databases produced 10,548 articles, of which 58 studies were included in the current study. We assessed the correlation of non-coding RNA (ncRNA) expression with different survival outcomes in breast cancer patients: overall survival (OS) (HR = 1.521), disease-free survival (DFS) (HR = 1.33), recurrence-free survival (RFS) (HR = 1.66), progression-free survival (PFS) (HR = 1.71), metastasis-free survival (MFS) (HR = 0.90), and disease-specific survival (DSS) (HR = 0.37). After eliminating low-quality studies, the results did not change significantly. In the diagnostic part, 22 articles and 30 datasets were retrieved from 8,453 articles. The quality of all studies was determined. The bivariate and random-effects models were used to assess the diagnostic value of ncRNAs. The overall area under the curve (AUC) of ncRNAs in differentiated patients is 0.88 (SENS: 80% and SPEC: 82%). There was no difference in the potential of single and combined ncRNAs in differentiated BC patients. However, the overall potential of microRNAs (miRNAs) is higher than that of long non-coding RNAs (lncRNAs). No evidence of publication bias was found in the current study. Nine miRNAs, four lncRNAs, and five gene targets showed significant OS and RFS between normal and cancer patients based on pan-cancer data analysis, demonstrating their potential prognostic value. Conclusion: The present umbrella review showed that ncRNAs, including lncRNAs and miRNAs, can be used as prognostic and diagnostic biomarkers for breast cancer patients, regardless of the sample sources, ethnicity of patients, and subtype of breast cancer.

Cancer Is Associated with the Emergence of Placenta-Reactive Autoantibodies.

Placenta-specific antigens are minimally expressed or unexpressed in normal adult tissues, while they are widely expressed in cancer. In the course of carcinogenesis, a vast array of autoantibodies (AAbs) is produced. Here, we used a quantitative approach to determine the reactivity of AAbs in the sera of patients with breast (BrC: N = 100, 100% female, median age: 51 years), gastric (GC: N = 30, 46.6% female, median age: 57 years), bladder (BC: N = 29, 34.4% female, median age: 57 years), and colorectal (CRC: N = 34, 41.1% female, median age: 51 years) cancers against first-trimester (FTP) and full-term placental proteome (TP) in comparison with age- and sex-matched non-cancer individuals. Human-on-human immunohistochemistry was used to determine reactive target cells in FTP. The effect of pregnancy on the emergence of placenta-reactive autoantibodies was tested using sera from pregnant women at different trimesters of pregnancy. Except for BC, patients with BrC (p < 0.0284), GC (p < 0.0002), and CRC (p < 0.0007) had significantly higher levels of placenta-reactive AAbs. BrC (p < 0.0001) and BC (p < 0.0409) in the early stages triggered higher autoantibody reactivity against FTP. The reactivities of BrC sera with FTP did not show an association with ER, PR, or HER2 expression. Pregnancy in the third trimester was associated with the induction of TP- and not FTP-reactive autoantibodies (=0.018). The reactivity of BrC sera with placental proteins was found to be independent of gravidity or abortion. BrC sera showed a very strong and specific pattern of reactivity with scattered cells beneath the syncytiotrophoblast layer. Our results reinforce the concept of the coevolution of placentation and cancer and shed light on the future clinical application of the placental proteome for the non-invasive early detection and treatment of cancer.

TMPRSS2 polymorphism (rs12329760) and the severity of the COVID-19 in Iranian population.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the recent pandemic since early 2020. Due to the wide range of clinical symptoms of this disease, from asymptomatic to severe and critical forms, it seems that genetic differences among patients, along with other factors (such as gender, age, and underlying diseases), can explain part of the variation in disease symptoms. The TMPRSS2 enzyme plays a vital role in the early stages of the interaction of the SARS-CoV-2 with the host cells by facilitating viral entry. There is a polymorphism in the TMPRSS2 gene, called rs12329760(C to T) as a missense variant, which causes the replacement of valine to methionine in the TMPRSS2 protein at position 160. The present study investigated the association between the TMPRSS2 genotype and the severity of the Coronavirus disease 2019 (COVID-19) in Iranian patients. The TMPRSS2 genotype of 251 COVID-19 patients (151 patients with asymptomatic to mild and 100 patients with severe to critical symptoms) was detected on genomic DNA extracted from patients' peripheral blood via the ARMS-PCR method. Our results showed a significant association between the minor T allele and the severity of the COVID-19 (P-value = 0.043) under the dominant and additive inheritance model. In conclusion, the results of this study showed that the T allele of the rs12329760 in the TMPRSS2 gene is a risk allele for severe form of COVID-19 in Iranian patients in contrast to most previous studies on this variant in European ancestry populations which suggested this variant as a protective allele. Our results reiterate to the ethnic-specific risk alleles and hidden unknown complexity behind the host genetic susceptibility. However, further studies are needed to address the complex mechanisms behind the interaction of the TMPRSS2 protein and the SARS-CoV-2 and the role of rs12329760 polymorphism in determining the disease severity.

Mortality Risk Related to Heatwaves in Dezful City, Southwest of Iran.

Background: We aimed to evaluate the impact of heatwaves on daily deaths due to non-accidental, cardiovascular and respiratory causes in the city of Dezful in Iran from 2013 to 2019. Method: We collected daily ambient temperature and mortality and defined 2 types of heatwaves by combining daily temperature ⩾90th in each month of the study period or since 30 years with duration ⩾2 and 3 days. We used a distributed lag non-linear model to study the association between each type of heatwave definition, and deaths due to non-accidental, cardiovascular and respiratory causes with lags up to 13 days. Results: There was no discernible correlation in this area, despite the fact that heatwaves raised the risk of death from cardiovascular causes and lowered the risk from respiratory causes. On the other hand, the risk of total non-accidental mortality on days with the heatwaves is significantly higher than normal days. In main effects, the heatwaves have a significant relationship with the risk of total non-accidental mortality (in the first heatwave definition, Cumulative Excess Risk (CER) in lag0-2 was 10.4 and in second heatwave definition, CER values in lag0, 0-2, and 0-6 were 12.4, 29.2, and 38.8 respectively). Also, in added effects, heatwaves have a significant relationship with the risk of total non-accidental mortality (in the first heatwave definition, CER in lag0 and 0-2 were 1.79 and 4.11 and in the second heatwave definition, CER values in lag0, 0-2, and 0-6 were 7.76, 18.35 and 24.87 respectively). In addition, heatwaves appeared to contribute to a cumulative excess risk of non-accidental death among the male group as well as the older adults. Conclusion: However, the results showed that heatwaves could have detrimental effects on health, even in populations accustomed to the extreme heat. Therefore, early warning systems which monitor heatwaves should provide the necessary warnings to the population, especially the most vulnerable groups.

The immunomodulatory effects of all-trans retinoic acid and docosahexaenoic acid combination treatment on the expression of IL-2, IL-4, T-bet, and GATA3 genes in PBMCs of multiple sclerosis patients.

OBJECTIVES: Multiple sclerosis (MS) is a potentially disabling autoimmune disease of the central nervous system. Neither the pathogenesis nor the effectiveness of treatment of MS has been fully understood. This in vitro trial evaluated the beneficial immunomodulatory effects of single and combined treatments of all-trans retinoic acid (ATRA) and docosahexaenoic acid (DHA) on the peripheral blood mononuclear cells (PBMCs) of relapsing-remitting MS (RRMS) patients who were receiving interferon beta (IFN-ß). METHODS: The PBMCs of 15 RRMS patients were isolated, cultured, and treated with single and combined treatments of ATRA and DHA. The expressions of IL-2, IL-4, T-bet, and GATA3 genes were evaluated using real-time PCR. RESULTS: The results showed that a single treatment of ATRA could significantly suppress the gene expression of the pro-inflammatory cytokine, IL-2 (P < 0.05), and related transcription factor, T-bet (P < 0.001). The gene expression level of the anti-inflammatory cytokine, IL-4, and its transcription factor, GATA3, were not significantly changed. The expression of IL-2 and T-bet genes was significantly decreased in combination treatments of ATRA and DHA (P < 0.001). Significant suppression of IL-2 and T-bet (P < 0.001) was observed in ATRA and DHA combination therapy with half doses of their single treatment, which suggested a synergistic effect of these components. DISCUSSION: Co-administration of vitamin A and DHA, an omega-3 fatty acid derivative, may exert a synergistic effect in modulating the immune system in MS patients; however, more studies are needed to evaluate the exact effects and mechanism of their actions on the immune cells.